Alfuzosin Treatment in Children and Adolescents With Hydronephrosis of Neuropathic Etiology (Alfahydro)

12-week, Multicenter, Open-label, Non-comparative Study to Investigate Pharmacodynamic and Safety of Alfuzosin 0.2 mg/kg/Day in the Treatment of Children and Adolescents 2 - 16 Years of Age With Hydronephrosis Associated With Elevated Detrusor Leak Point Pressure of Neuropathic Etiology Followed by a 40-week Open-label Extension

Primary objective was to determine efficacy of Alfuzosin in the treatment of children and adolescents 2-16 years of age with newly diagnosed or progressive hydronephrosis due to elevated detrusor Leak Point Pressure [LPP] of neuropathic etiology.

Secondary objectives were:

• To investigate the safety and tolerability of alfuzosin 0.2 mg/kg/day in children and adolescents,
• To investigate the number of Urinary Tract Infection (UTI) episodes,
• To investigate the pharmacokinetics of Alfuzosin (population kinetics).

Study Overview

• Status: Completed
• Conditions: Hydronephrosis; Neurogenic Bladder
• Intervention / Treatment: Drug: Alfuzosin

Detailed Description

The study consisted of 2 phases:

• a 12-week efficacy phase then,
• a 40-week safety extension phase.

All eligible subjects received alfuzosin 0.2 mg/kg/day. The formulation and the frequency was assigned by Interactive Voice Response System (IVRS) according to age group and ability to swallow tablets.

Patients who completed the 12-week open-label treatment period were offered to continue in the 40-week open-label safety extension study. The treatment was the same as in the 12-week efficacy phase.

All patients had a one-week follow-up period after the last dose intake.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • Sanofi-Aventis Administrative Office
• Canada
  • Laval, Canada
    • Sanofi-Aventis Administrative Office
• Estonia
  • Tallin, Estonia
    • Sanofi-Aventis Administrative Office
• India
  • Mumbai, India
    • Sanofi-Aventis Administrative Office
• Malaysia
  • Kuala Lumpur, Malaysia
    • Sanofi-Aventis Administrative Office
• Poland
  • Warszawa, Poland
    • Sanofi-Aventis Administrative Office
• Russian Federation
  • Moscow, Russian Federation
    • Sanofi-Aventis Administrative Office
• Serbia
  • Belgrade, Serbia
    • Sanofi-Aventis Administrative Office
• Singapore
  • Singapore, Singapore
    • Sanofi-Aventis Aministrative Office
• Slovakia
  • Bratislava, Slovakia
    • Sanofi-Aventis Administrative Office
• Taiwan
  • Taipei, Taiwan
    • Sanofi-Aventis Administrative Office
• Turkey
  • Istanbul, Turkey
    • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children and adolescents of either gender 2 - 16 years of age with a detrusor Leak Point Pressure (LPP) of 40 cm water or greater and with newly diagnosed or progressive hydronephrosis either Society of Fetal Urology (SFU) grade 1, 2 or 3 due to neuropathic bladder dysfunction.

Exclusion Criteria:

• Hydronephrosis of non-neuropathic etiology.
• Urological surgery in the last 4 months prior to the study.
• Urethral dilatation in the last 3 months prior to the baseline urodynamic assessment.
• α-blocker therapy in the last 4 weeks prior to the baseline urodynamic assessment.
• Detrusor injections of botulinum toxin in the last 6 months.
• Urological diseases/conditions other than functional bladder obstruction of neuropathic etiology, that can lead to upper urinary tract dilatation (e.g., bladder anomalies, ureterocele).
• History of intolerance to α-blocker therapy.
• Orthostatic hypotension.
• History of risk factors for Torsade de pointes (e.g., family history of Long QT Syndrome).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alfuzosin solution - 2-7 years; Alfuzosin solution, daily dose divided in 3 doses given at breakfast, lunch and dinner to children 2-7 years of age.	Drug: Alfuzosin; Dose: 0.2 mg/kg/day Route: oral; Other Names: SL770499
Experimental: Alfuzosin solution - 8-16 years; Alfuzosin solution, daily dose divided in 3 doses given at breakfast, lunch and dinner to children and adolescents 8-16 years of age who were not able to swallow tablets or preferred to take the solution or had a body weight < 30 kg.	Drug: Alfuzosin; Dose: 0.2 mg/kg/day Route: oral; Other Names: SL770499
Experimental: Alfuzosin tablet - 8-16 years; Alfuzosin tablet, daily dose divided in 2 doses given at breakfast and dinner to children and adolescents 8-16 years of age who were able to swallow tablets and had a body weight ≥ 30 kg.	Drug: Alfuzosin; Dose: 0.2 mg/kg/day Route: oral; Other Names: SL770499

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Decrease From Baseline ≥ 1 in the Society of Fetal Urology (SFU) Grade of Hydronephrosis	Hydronephrosis was investigated by ultrasound and graded using SFU classification at each time point. 'Complete response' was assessed when bilateral hydronephrosis at baseline and grade decrease from baseline ≥ 1 for both kidneys, or, unilateral hydronephrosis at baseline and grade decrease from baseline ≥ 1 for the affected kidney without worsening of the other kidney. 'Partial response' was assessed when bilateral hydronephrosis at baseline and grade decrease from baseline ≥ 1 for one kidney without worsening of the other kidney.	baseline and 12 weeks (efficacy study phase)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes	When a patient presented with symptoms such as pain, fever or hematuria (discretion of the Investigator), an urinalysis was performed including a dipstick and a quantitative urine culture. A symptomatic UTI was defined as the presence of symptoms and a positive culture with > 100 000 Colony Forming Units (CFUs) with a single organism.	12 weeks (efficacy study phase)
Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes		52 weeks (efficacy and extension study phases)

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: December 18, 2007
• First Submitted That Met QC Criteria: December 18, 2007
• First Posted (Estimate): December 19, 2007

Study Record Updates

• Last Update Posted (Estimate): October 29, 2014
• Last Update Submitted That Met QC Criteria: October 21, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: child; bladder; neuropathic; alpha blockers
• Additional Relevant MeSH Terms: Nervous System Diseases; Kidney Diseases; Urologic Diseases; Urinary Bladder Diseases; Neurologic Manifestations; Urinary Bladder, Neurogenic; Hydronephrosis; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Alfuzosin
• Other Study ID Numbers: EFC6269; 2004-002397-38 (EudraCT Number); SL770499